Saints fell to a 0-1 home defeat to Motherwell after a Devante Cole goal in the first-half gave the Steelmen all three points.
A Scott Tanser missed penalty in the second-half compounded the misery for Saints who are still searching for the first league win of the season.
Drey Wright retuned to the starting XI for the first time since his injury against Kilmarnock last November with Jason Holt also returning to the squad. Matty Kennedy and David Wotherspoon were the two players who made way.
Saints kicked off in the McDiarmid Park sun and it was a positive start from Tommy Wright's men in the opening stages.
Stevie May had the first effort the game following a Tanser free-kick but his shot was tipped over the crossbar by Gillespie. Liam Gordon got his head on a Jason Holt corner but the ball drifted wide of the target.
Murray Davidson was the next to have a go but his header was gathered lacked pace and was gathered comfortably by Gillespie.
Despite good early pressure from Saints it was Motherwell who should have gone ahead after 15 minutes.
James Scott did well in the box to shift past Tanser before drilling a low ball across goal for Devante Cole who somehow managed to miss the target despite having a tap-in from within four-yards.
Motherwell captain Hartley was the first player in referee Gavin Duncan's book following a trip on Davidson but Saints couldn't capitalise on the free-kick.
Saints came close again in the 39th minute when Jason Holt’s corner found the head of Jason Kerr but his effort was wide of the target.
Motherwell forced a corner after a long range effort deflected off Ali McCann with just a few minutes of the first-half remaining.
From the corner, Declan Gallagher rose above the rest to head the ball back across goal into the six-yard-box and it fell to Devante Cole who made no mistake this time around and put the visitors ahead.
There was only one change at half-time as Sherwin Seedorf was replaced by Jermaine Hylton.
Saints had a golden opportunity to equalise at the beginning of the second-half as Ralston cross on 51 minutes was met by May yards out but the striker couldn't connect properly and his appeals for a penalty were waved away by the referee.
Just moments later, Murray Davidson was pushed in the box after rising to win a header and this time Gavin Duncan had to hesitation in pointing to the spot.
Scott Tanser stepped up - who had a 100% record since taking over penalties - but his effort was a great height for Gillespie who made the save to deny Saints an equaliser.
The miss gave Motherwell a short lift as they forced some corners and tried to put Saints under pressure in pursuit of a second which would have made it more comfortable for Stephen Robinson's men.
Michael O’Halloran was replaced by Matty Kennedy, and Danny Swanson came on for Ali McCann as Saints went in search for an equaliser.
Davidson continued to cause a threat and came agonisingly close to meeting a header in the box following a Swanson corner but again the chance wasn't taken.
In the 75th minute Drey Wright was replaced by Chris Kane and the Manager altered his formation to 4-4-2.
Peter Hartley was the next to have an attempt on gaol finding himself free in the Saints box his placed header was saved in the corner of his goal by Zander Clark.
An alert Zander Clark kept Saints in the game as Jason Kerr was caught out with a short pass back but the visitors failed to capitalise.
Saints continued to press and the substitute Matty Kennedy was tormenting the visiting defence. His cross on 87 minutes was met by Davidson who’s header went narrowly wide and within a minute the winger was at it again, crossing this time for Stevie May who saw his goal-bound effort tremendously saved by Gillespie.
Three minutes of injury time came and went with Saints having one final chance to grab an equaliser.
An off the ball clash in the dying seconds saw Liam Donnelly receive a red card but the resulting free kick from Danny Swanson was claimed in the air by Mark Gillespie before the referee blew his full-time whistle seconds later.
Saints: Clark, Ralston , Kerr, Gordon, Tanser, Wright (Kane 75), McCann (Swanson 67), Holt, O’Halloran (Kennedy 63), Davidson, May,
Unused Subs: Parish, Duffy, Booth, Wotherspoon
Motherwell: Gillespie, Hartley, Gallagher, Tait, Grimshaw, Donnelly, Campbell, Polworth, Cole (Long 83), Scott (Ilic 66), Seedorf (Hylton 45)
Unused Subs: Carson, Maguire, o’Hara, Mugabi
Referee: Gavin Duncan
Assistants: Kylie Cockburn and Ross Macleod
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